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After ten years, the tsetse genome has been mapped

TDR news item 25 April 2014

A new paper published in Science reports that the genetic code of Glossina morsitans, one of 32 species of tsetse fly that are vectors of trypanosomiasis, also known as sleeping sickness, has been sequenced and annotated, providing researchers with a wealth of new information and making possible much needed improvements in control of the deadly disease.

"We also wanted to use the project as a platform to build research capacity in developing countries around the vector and the disease ̶ and that’s where TDR was extremely helpful."

Dr Serap Aksoy, Yale University

The paper is the culmination of a decade of work by nearly 150 scientists — half of them from African institutions — under the aegis of the International Glossina Genome Initiative (IGGI). Established in 2004 with seed funding from the World Health Organization, the Wellcome Trust and TDR, the initiative set out to map the genetic blueprint of a rather unusual insect – a fly that feeds exclusively on vertebrate blood, gives birth to very large live young, one at a time, and nurses its young through lactation.

“When I first learned about tsetse, I found it hard to believe that it was any good at being a vector,” says Dr Matt Berriman, a group leader at the Wellcome Trust Sanger Institute and one of the lead authors on the paper. “It seemed that you wouldn’t have to do much to interfere with their biology.” While sequencing the genome of an organism may not in itself be seen as anything new, he says, “in the case of tsetse, where you have so much to explore and exploit, it was the critical first step.”

Ten years ago, it was also a very expensive first step. “The main obstacle was the funding,” says Dr Serap Aksoy, a vector biologist at Yale University, and also a lead author on the paper. “The old sequencing methodologies were very costly, and given the neglected nature of the disease, it didn’t fit the bill for a major grant. So from the start, we knew it would be a challenge to fund the project.”

Aksoy adds that although sequencing the tsetse genome was always the ultimate goal, “we also wanted to use the project as a platform to build research capacity in developing countries around the vector and the disease -- and that’s where TDR was extremely helpful.” In addition to providing partial funding for the sequencing and annotation, TDR support made it possible for the consortium to meet annually and to conduct small side projects aimed at incorporating African scientists. “Every year, the meeting got larger and larger, and I think that really helped forge a community.”

According to TDR scientist Yeya Touré, the IGGI marks a first for TDR. “We were supporting genomics activities before this effort to sequence Glossina morsitans,” he says, “but this was the first such project in which African countries were intimately involved from the very beginning.” And that early involvement makes all the difference, he says.

In addition to strengthening capacity in African institutions, those side projects also compelled the Sanger Institute to up its involvement in the initiative. Over the past ten years, the Sanger Institute’s contributions to sequencing and annotation activities have amounted to roughly $4 million. Given the burden of African trypanosomiasis on human health, says Berriman, that was money well spent.

“Now that so many things have been sequenced, people are hungry for that exploitable brand new thing,” Berriman adds. “But actually mapping out all of the tsetse’s metabolism, and understanding the molecular underpinnings of things we already know about the vector, is very important here.” Whereas previously, the starting point for a biology project in tsetse might have meant blindly searching for an early lead,” Berriman explains, “that work is now done for everyone.

Yeya Touré adds, “You can use this information to identify genetic markers and better understand things like the fly’s immune response to parasites and pathogens and what genes are involved in host-seeking behavior. And that knowledge can then be used to enhance trapping systems and other control methods.”

The work initiated additional efforts to sequence other Glossina species. “Glossina morsitans has served as a scaffold for our other projects,” says Aksoy. The IGGI consortium recently received funding from the US National Institutes of Health to sequence and annotate four other species in the Glossina genus as well as the common housefly. “And this comparative genomics will be very interesting for the consortium to delve into.”